TIRILAZAD MESYLATE PROTECTS STORED ERYTHROCYTES AGAINST OSMOTIC FRAGILITY

The hypoosmotic lysis curve of freshly collected human erythrocytes is consistent with a single Gaussian error function with a mean of 46.5 +/- 0.25 mM NaCl and a standard deviation of 5.0 +/- 0.4 mM NaCl. Afte r extended storage of RBCs under standard blood bank conditions the ly sis curve conforms to the sum of two error functions instead of a poss ible shift in the mean and a broadening of a single error function. Th us, two distinct sub-populations with different fragilities are presen t instead of a single, broadly distributed population. One population is identical to the freshly collected erythrocytes, whereas the other population consists of osmotically fragile cells. The rate of generati on of the new, osmotically fragile, population of cells was used to pr obe the hypothesis that lipid peroxidation is responsible for the indu ction of membrane fragility. If it is so, then the antioxidant, tirila zad mesylate (U-74,006f), should protect against this degradation of s tored erythrocytes. We found that tirilazad mesylate, at 17 mu M (1.5 mol% with respect to membrane lecithin), retards significantly the for mation of the osmotically fragile RBCs. Concomitantly, the concentrati on of free hemoglobin which accumulates during storage is markedly red uced by the drug. Since the presence of the drug also decreases the am ount of F-2-isoprostxanes formed during the storage period, an antioxi dant mechanism must be operative. These results demonstrate that tiril azad mesylate significantly decreases the number of fragile erythrocyt es formed during storage in the blood bank.